Chromatography columns

ABSTRACT

The present invention relates to a chromatography column that removes the longitudinal load from the column tube altogether and transfers it to a yoke and stanchion arrangement situated around but external to the column tube. By using the yoke/stanchion system, the central adjuster can be used to move the top end into and out of the housing. Thus, when internal pressure is applied to the column, the tube experiences no longitudinal load. Additionally, the yoke and stanchion design allows for complete removal of the end from the tube without cumbersome disassembly. Moreover, the yoke provides a place to retain the end while the tube is being filled, emptied, cleaned or repaired.

CROSS-REFERENCE RELATED APPLICATIONS

This application is a Divisional application of U.S. application Ser.No. 11/325,205, filed on Jan. 4, 2006, which is a Divisional applicationof U.S. application Ser. No. 10/373,293, filed on Feb. 24, 2003, whichclaims the benefit of U.S. Provisional Application No. 60/361,483, filedon Mar. 4, 2002. The entire contents of the related application areincorporated in their entirety.

BACKGROUND OF THE INVENTION

Chromatography columns have been used for years for the separationand/or purification of different materials such as proteins.

These columns are formed of three basic components; a column tube, abottom fixed end and a top, movable end. See U.S. Pat. No. 4,350,595 andU.S. Pat. No. 6,139,732. The top end moves relative to the tube so as tobe capable of removal for introduction and removal of chromatographymedia in the tube and to be capable of longitudinal travel into the tubeto compress the media for use.

This top end however needs to be fixed at some point to the column inorder to move relative to the column.

A first means for accomplishing this is to form a tube of high strengthmaterials, including metals such as stainless steel or rigid structuralplastics, such as acrylics or polymethylpentenes such as TPX® plasticavailable from Mitsui Petrochemical Industries Ltd Corporation of Japan.The tube has a flange at the upper end to which a top plate is attachedto the column and a flange at the lower end to which a fixed bottom endis attached. The top, movable end is then attached to this top plate andtravels relative to it in and out of the tube.

An example of this type of structure is shown in FIG. 1. The tube 2 hasa bottom plate 4 fixed in place by bolts 6 attached to a flange 8 of thetube 2. A top plate 10 is fixed to a top flange 12 of the tube 2 bysetscrews 13. A movable end 14 is centrally located in the top plate 10and is capable, by movement of rod 16, of moving into or out of the tube2.

As the end 14 moves into the tube 2 to compress the media bed 18 foruse, longitudinal forces are carried from the end 14 to the rod 16 tothe top plate 10 and then to the tube 2 itself.

The other alternative is shown in FIG. 2. It uses a series of rods 20 orscrews closely aligned around the outside of the tube 24 to carry thelongitudinal forces rather than the wall of the tube itself. This allowsone to use less structurally rigid materials, such as glass or plastics,preferably acrylic or styrene, and to also use thinner walled tubes. Allof this reduces the weight and cost of the device.

Most of the elements of that tube 24 of FIG. 2 are similar to those ofFIG. 1. One has a movable top end plate 22, a bottom plate 26, attachedto a fixed bottom end 27, flanges 28, either as part of the tube 24 orin this example as separate pieces to secure the fixed top plate 30 andbottom plate 26 to the tube 22. A rod 32 extends through the plate 30and is connected to the movable end 22 by a handle 34. A bed ofchromatography media 36 is compressed by the movement of the end 22.Also shown in FIG. 2 are a series of guide rods 36, which are used, inlarger columns to keep the end 22 horizontal during movement. Plate 30is normally affixed on flange 33 and attached by numerous mechanicalfasteners 31.

Both of these designs have their limitations. The need to use rigidstructural materials for the tube in the embodiment of FIG. 1 limitsone's choices of materials and often is more expensive. Also, thematerials used are not translucent so that one cannot view the interiorof the column. Removing the movable end from the column, such as to addor remove media is a cumbersome task requiring the removal of the topplate and bolts in order to do so. Also, once removed, one must find aplace to position these pieces (top plate 10, rod 16 and end 14) wherethey will not be damaged or contaminated.

The embodiment of FIG. 2 provides one with the ability to usetranslucent materials such as glass or acrylic; however, the rods (whichtypically number between 8 and 12 per column) obscure one's view.Moreover, it is even more cumbersome to disassemble. One must disconnectall of the mechanical fasteners 31 from the ends of the rods 20 beforeremoving the top plate 30 and end assembly (22, 32, 34). It too suffersfrom having to find a place to put these pieces where they will not bedamages or contaminated. Further, reassembly is difficult, as one needsto align each of the mechanical fasteners 31 into their respective holein the top plate 30 and flange 33.

What is needed is a simpler and easier mechanism for handling thelongitudinal load of a column and which allows one to easily assembleand disassemble the column as needed.

The present invention provides such a device.

SUMMARY OF THE INVENTION

The present invention relates to a chromatography column. Moreparticularly, it relates to a chromatography column that utilizes anexternal structure to support any longitudinal loads imposed on thecolumn.

The present invention removes the longitudinal load from the column tubealtogether and transfers it to a yoke and stanchion arrangement situatedaround but external to the column tube. By using the yoke/stanchionsystem, the central adjuster can be used to move the top end into andout of the housing. Thus, when internal pressure is applied to thecolumn, the tube experiences no longitudinal load. Additionally, theyoke and stanchion design allows for complete removal of the end fromthe tube without cumbersome disassembly. Moreover, the yoke provides aplace to retain the end while the tube is being filled, emptied, cleanedor repaired.

It is an object of the present invention to provide a chromatographycolumn comprising a base plate, a column tube attached to the base platein a liquid tight arrangement, a movable top plate capable of movinginto and out of the tube and a support structure external of the tubeand free of support on the tube to support longitudinal loads imposed onthe column.

It is another object of the present invention to provide achromatography column comprising a base plate, column tube, a bottomedge of the tube being attached in a liquid tight sealing arrangement tothe base plate, the base plate having diameter greater than that of thetube, two or more stanchions, each having a lower end and an upper end,the lower ends being attached to the base plate external of the tube, ayoke connected to the two or more stanchions such that it spans thewidth and centerline of the tube, a central adjuster is formed on theyoke over the centerline of the tube, the adjuster being movablyconnected to a top surface of a column top end plate so that the top endplate may move into and out of the tube interior.

It is a further object of the present invention to provide achromatography column using an external set of stanchions and a yokeconnected to the stanchions to carry any longitudinal load imposed onthe tube of the column and to provide a yoke that is capable of pivotingvertically, horizontally or both about the centerline of the column tubeso as to provide free and easy access to the column tube's interior.

It is an additional object of the present invention to provide achromatography column using an external set of stanchions and a yokeconnected to the stanchions to carry any longitudinal load imposed onthe tube of the column and to provide a column that allows for theremoval or repair of the top plate, tube or bottom plate of the columnwithout complete disassembly of the column.

It is another object of the present invention to provide a modularchromatography column having a base plate capable of holding columntubes of varying sizes and heights, using an external set of stanchionsconnected to the base plate and a yoke connected to the stanchionswherein the stanchions are formed of two or more pieces and are capableof being adjusted in height by the addition or subtraction of one ormore pieces of the stanchions.

IN THE DRAWINGS

FIG. 1 shows a first embodiment of a prior art column in cross sectionalview.

FIG. 2 shows a second embodiment of a prior art column in crosssectional view.

FIG. 3 shows a first embodiment of the present invention in planar view.

FIG. 4 shows the embodiment of FIG. 3 in a retracted/pivoted position.

FIG. 5 shows the embodiment of FIG. 3 in cross sectional view.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 3 shows a first embodiment of the present invention. Thechromatography column consists of a base plate 50 to which the bottomedge of the tube 52 is attached.

One can form a flange (not shown) on the bottom edge of the tube, ifdesired, either as a part of the tube or separately. Unlike in the priorart, as the tube does not bear any longitudinal load, the flange doesnot need to have significant structural strength, thus one can easilymake a flange on an acrylic or glass column.

Alternatives to the flange can be used to secure the bottom of the tubeto the base plate 50.

The base plate 50 has diameter greater than that of the tube 52.Arranged around the base plate 50, external to the tube 52 are two ormore stanchions 54. The stanchions are structurally strong and typicallyformed of engineered materials that provide such strength such asmetals, including stainless steel and aluminum, composites such asgraphite or carbon composites and engineered plastics or compositeplastics.

The stanchions 54 have a height equal to or greater than that of thetube 52. Preferably, they have a height that is greater than the tube52.

A yoke 56 is connected to the two or more stanchions and it spans thewidth and centerline of the tube 50. The yoke 56 is retained to thestanchions 54 by means such as slot 58 (as shown), a ring or otherdevice that can affirmatively hold the yoke in place. A central adjuster60 is formed in the yoke 56 over the centerline of the tube 52. Theadjuster 60, as shown, uses a screw-threaded rod 62 connected to the topsurface 64 of the movable end 66. This central adjuster 60 is used tochange the height of the movable end 66 within the tube 52.

The yoke 56 may be permanently attached to the two or more stanchions 54or if one wishes, it may be removably connected to the stanchions 54 bybolts, clevis pins, cotter pins, clamps and the like. In one preferredembodiment, the yoke 56 is attached to one stanchion 54 by a bolt andthe other stanchion by a clevis pin so that when the end 66 is withdrawnfrom the column by retracting the central adjuster 60 to its uppermostposition, the yoke 56 can be pivoted vertically about the stanchion 54containing the bolt and moved up and out of the way of the tube 50 so asto allow easy access to the column interior. FIG. 4 shows thatembodiment in the retracted/pivoted position.

Alternatively, one can form hooks, eyelets or openings (not shown) in oron the yoke 56 such that one may use a crane, come along winch or othersuch winching device to vertically lift the yoke 56, central adjuster 60and end 66 off of the system in order to provide access to the columninterior.

In another embodiment, the yoke 56 can also rotate in a horizontalcircular motion away from the mouth of the column.

In a further embodiment, the yoke 56 can be detachable from all but onestanchion 54. That stanchion 54 is of a height that the end 66 is out ofthe tube 52 when the central adjuster 60 is fully retracted. The yoke 56does not pivot vertically. The stanchion 54 however is capable ofhorizontal, circular motion away from the tube.

If desired, one may form a stop (not shown) on the yoke 56 or stanchion54 about which it rotates vertically so as to limit the yoke's 56 rangeof motion so that it does not pivot to a position where the yoke 56 orend 66 can be damaged.

In a further embodiment, the yoke 56 remains fixed to the one or morestanchions 54. The stanchions 54 have a height that is greater than theheight of the tube 52 so that the end may be fully removed from the tube52 and provide adequate space for one to enter the tube.

The central adjuster 60 may be manually, pneumatically, electrically orhydraulically adjustable between positions or a combination of actuationmethods maybe used. Non-manual actuation maybe preferable whenadditional force, speed or convenience is required.

As the tube wall of the column does not bear any of the longitudinalforces, the materials selected for the tube do not have to bestructurally supportive. Glass and various plastics can be used.Suitable plastics are preferably translucent to allow for the viewing ofthe interior of the column tube. Such plastics include but are notlimited to acrylics, styrene, polycarbonate and TPX® Polymethylpentene®resin. If desired, metals, such as stainless steel, and other materialstypically used in chromatography columns may also be used.

The tube may range in diameter from about 70 mm inner diameter to about450 mm inner diameter. Its height may also vary from about 500 mm toabout 1200 mm.

The base plate may be formed of a metal such as stainless steel,aluminum and the like, a structurally rigid plastic such as TPX plasticor a composite material such as graphite or carbon composite materials.

The diameter of the base plate should be large enough so as toaccommodate the column and the stanchions. Preferably, it is circular inshape, to mirror the column, but it need not be so limited. It may be apolygonal shape such as a square, rectangle, pentagon, hexagon, decagonand the like. Alternatively, it may be irregular, providing sufficientarea for the column and then having two or more ears extending from iton which the stanchions are mounted.

The stanchions may be formed of any material that provides the necessarystrength required. Metals, such as stainless steel, epoxy-coated steeland aluminum are preferred, while engineered plastics such as TPX®plastic or graphite or carbon composites may be used.

Depending upon the load to be supported by the stanchions, they may besolid or hollow. They may also be formed as one piece or if desiredseveral pieces, which are connected together by means such as bolts,clevis pins, mating screw threads and the like. The multiple piecestanchions would allow one to vary the height of the stanchions inrelation to the column and would allow one to have a modular column inwhich different tubes of different heights and/or diameters could beused with a single base and stanchions that are capable of being variedin height.

The stanchions are secured to the base by a variety of means such aswelding, bolts, and the like.

FIG. 5 shows preferred chromatography system according to the presentinvention in cross-sectional view, as it would be used in a lab or on aproduction floor.

The system 1100 is comprised of a base 102 that is supported on three ormore legs 104. Each leg 104 has a caster wheel 106 on its lower end. Thecaster wheel 106 may have a lockable brake (not shown) if desired. Thebase 102 contains a closable opening 108, which forms either an inlet oroutlet of the column. In another embodiment, the inlet or outlet oneither the central adjuster or base is a more complex valve as disclosedin U.S. Pat. No. 6,123,849. The column tube 110 is mounted on top of thebase 102 and secured to it by a series of two or more bolts 112.

Surrounding the tube 100 are two or more stanchions 114. The two or morestanchions 114 are spaced apart from the tube 110 and have a heightgreater than that of the tube 110. If two stanchions 114 are used, theyare diametrically opposite each other. If more than two are used, theyare equally spaced about the tube 110. In that embodiment, the yoke 116will also be formed of several equal arms running from a stanchion 114to the central adjuster 118. In embodiment of FIG. 5, two stanchions 114being used, the yoke 116 is a straight single piece, formed of two armsin alignment with each other end meeting at the central adjuster 118.

As shown, the central adjuster has a threaded rod 120 that mates withfixed threads of the adjuster 118. A preferred mechanism is a threadedthrust ring 119 although other means may be used. A rotatable handle 122is used to move the rod 120 via rotation of its threads against thosefixed threads of the adjuster 118.

The lower end of the rod 118 is attached to the movable end plate 124via a series of equally spaced arms 126 that distribute the forceequally around the top of the end plate 124. Alternatively, one couldeliminate those arms 126 if they were deemed unnecessary or if otheralignment mechanisms were used instead.

The yoke 116 is fixed at each end to the respective stanchions 114 by alocking device 127 such as a nut and bolt, a clevis pin, a spring loadedball and detent system and the like. As stated above, the yoke 116 mayinstead be permanently fixed to the stanchions 114, such as by formingthe stanchions and yoke of a single piece of material or by welding oradhering the components together. It is preferred however that the yoke116 be capable of being removed from the stanchions 114 for versatilitysake.

A cap 128 may be used over the top of the stanchions 114 after the yoke114 is in place.

Also as shown in FIG. 5, the yoke 116 has an upwardly tapered profile incross-section. This is desired but not necessary. The use of a taperedyoke 116 provides additional strength with little material or cost.Alternatively, one could use a linear yoke 116 and make its thicknessgreater in order to achieve the same result. If desired, the yoke can beforged, machined from a single piece, molded to be a structural beam ofregular or irregular shape, formed of a lamination of materials orformed of a series of thinner layers bolted or welded together. Astructural beam or laminated beam would be lighter in weight and lowercost and provide all the force transferring properties necessary for theinvention.

The top lip of the tube 110 has an optional end plate guide 130 that isused to direct and align the end plate 124 as it moves into and out ofthe tube 110.

The end plate 124 is typical of that used in a chromatography column andcontains a backer plate 132 and a distributor plate 134 and an upperfrit or distributor screen 136.

The stanchions 114 are attached to the base 102 and into a threadedrecess in the bottom portions of the stanchions 114.

A device as shown in FIG. 5 is operated in the following manner. To loadthe column, the central adjuster 118 is retracted so that the end plate124 is out of the tube 110. If desired, the yoke 116 has either beenpivoted out of the way or it may be removed altogether as explainedabove.

The media is placed within the column. If the yoke 116 had been pivotedor removed, it is reattached to the stanchions 114. The end plate 124 isthen driven down into the tube 110 past the guide ring 130 by thecentral adjuster 118. The end plate is adjusted to the desired height,given the type and amount of media used and the desired pressures to beapplied.

The chromatography process is run, the captured material eluted and thesystem is flushed.

To open the column, for example to remove the media, the end plate 124is retracted from the tube 114 and either left hanging from the yoke 116above the tube or the yoke is either then pivoted away or removedaltogether. The media is then removed either through the top opening ofthe tube or if desired, through the fixed plate which is arranged withthe base plate so as to be removable without the need to disassemble theentire column. This embodiment allows one to simply push the spent mediaout of the bottom into a catch basin.

The various alternative embodiments presented by the present device arenearly endless.

The present invention allows one to use a common base for differentsized columns. For example, one could select a series of base plates ofvarying diameters that allows one to use column tubes of different sizeswith basically the same device. For example, the same base plate, yokeand top plate can be used with 70 mm, 100 mm and 1401 mm tubes. Thestanchions if of sufficient height would not need to be changed. Ifadditional height is required, one can use the multiple piece stanchionsdiscussed above. Alternatively, one can form a single base plate andhave an open in its center into which the end plate fits. Variousextensions or fixed end plate widths can be formed and used with thesame base plate to enable one to use columns of different diameters andheights.

Likewise, as discussed above, stanchions of different heights can becreated by using multiple piece stanchions, allowing one to use tubes ofdifferent heights with the same equipment.

Also the present invention allows one an easy means for removing orrepairing one component of the column without the difficult and timeconsuming task of disassembling the entire column as was required in theprior art.

As can be appreciated, the present invention provides a chromatographycolumn with several advantages over the prior art.

Through the use of the stanchions and yoke, one eliminates theimposition of longitudinal forces on the column itself. This allows forone to use lighter, less rigid materials for the column tube. It alsoeliminates the need for many rods attached to the outside of the column,thus making viewing access possible and eliminating the time consumingtask of aligning the rods during assembly and removing them duringdisassembly.

Additionally, by providing a yoke capable of being vertically pivotedand/or horizontally rotated or being capable of removal altogether, oneobtains a simple means for retaining the end plate in a position whereit is unlikely to be damaged or contaminated during maintenance orrepairs.

The system allows for a modular system where columns of differentheights or diameters can be used with the same basic equipment.

The system of the present invention allows one to remove or repair ofthe top plate, tube or bottom plate of the column without completedisassembly of the column.

1) A chromatography column comprising a base plate, a column tubeattached to the base plate in a liquid tight arrangement, a movable topplate capable of moving into and out of the tube and a support structureexternal of the tube and free of support on the tube to supportlongitudinal loads imposed on the column, a yoke connected to thesupport structure, the yoke having a central adjuster, the adjusterbeing movably connected to a top surface of the top plate so that thetop plate may move into and out of the tube and the yoke and column tubeare arranged so as to be pivoted away from each other when the columntop plate is out of the tube. 2) A chromatography column comprising abase plate, column tube, a bottom edge of the tube being attached in aliquid tight sealing arrangement to the base plate, the base platehaving diameter greater than that of the tube, two or more stanchions,each having a lower end and an upper end, the lower ends being attachedto the base plate external of the tube, a yoke connected to the two ormore stanchions such that it spans the width and centerline of the tube,a central adjuster is formed on the yoke over the centerline of thetube, the adjuster being movably connected to a top surface of a columntop end plate so that the top end plate may move into and out of thetube interior and the yoke and column tube are arranged so as to bepivoted away from each other when the column top end plate is out of thecolumn tube. 3) The column of claim 1 wherein the support structure iscomprised of two or more stanchions, each having a lower end and anupper end, the lower ends of the two or more stanchions being attachedto the base plate external of the tube and the yoke being connected tothe two or more stanchions such that it spans a width and centerline ofthe tube. 4) The column of claim 1 wherein the support structure iscomprised of two or more stanchions, each having a lower end and anupper end, the lower ends of the two or more stanchions being attachedto the base plate external of the tube, the yoke connected to the two ormore stanchions such that it spans a width and centerline of the tube,the central adjuster is formed on the yoke over the centerline of thetube, the adjuster being movably connected to a top surface of the topplate and the yoke is selectively attached to the two or more stanchionssuch that the yoke and column tube may pivot horizontally away from eachother. 5) The column of claim 1 wherein the support structure iscomprised of two or more stanchions, each having a lower end and anupper end, the lower ends of the two or more stanchions being attachedto the base plate external of the tube, the yoke connected to the two ormore stanchions such that it spans a width and centerline of the tube,the central adjuster is formed on the yoke over the centerline of thetube, the adjuster being movably connected to a top surface of the topplate, the yoke is selectively attached to the two or more stanchionssuch that it may be pivoted away from the centerline of the tube whenthe top plate has been retracted from the tube. 6) The column of claim 1wherein the support structure is comprised of two or more stanchions,each having a lower end and an upper end, the lower ends of the two ormore stanchions being attached to the base plate external of the tube,the yoke connected to the two or more stanchions such that it spans awidth and centerline of the tube, the central adjuster is formed on theyoke over the centerline of the tube, the adjuster being movablyconnected to a top surface of the top plate and wherein the yoke andcolumn tube are arranged so that the yoke and tube may be pivotedhorizontally away from teach other when the top plate has been retractedfrom the tube. 7) The column of claim 2 wherein the yoke and column tubeare arranged such that the yoke and tube may be pivoted horizontallyaway from each other when the top end plate has been retracted from thetube. 8) The column of claim 2 wherein the yoke is selectively attachedto the two or more stanchions such that it may be pivoted awayhorizontally from the centerline of the tube when the top plate has beenretracted from the tube. 9) A process for the maintenance of achromatography column comprising the steps of providing a chromatographycolumn having a base plate having a closable opening, column tube, abottom edge of the tube being attached in a liquid tight sealingarrangement to the base plate, the base plate having diameter greaterthan that of the tube, two or more stanchions, each having a lower endand an upper end, the lower ends being attached to the base plateexternal of the tube, a yoke connected to the two or more stanchionssuch that it spans the width and centerline of the tube, a centraladjuster is formed on the yoke over the centerline of the tube, theadjuster being movably connected to a top surface of a column top endplate so that the top end plate may move into and out of the tubeinterior and wherein the yoke and two or more stanchions removes thelongitudinal load from the column tube and transfers the load to theyoke and two or more stanchions and the yoke and column tube arearranged such that one is capable of being pivoted away from the otherwhen the top plate has been retracted from the tube, maintaining the topplate within the column tube during packing and chromatographicoperations, retracting the top plate from the column tube and pivotingthe yoke and column tube away from each other to provide access to theinterior of the column tube and performing maintenance on the column.10) The process of claim 9 wherein the yoke and column tube are pivotedaway from each other in a horizontal direction.